Methotrexate for maintenance of remission in Crohn's disease

  • Review
  • Intervention

Authors


Abstract

Background

Safe and effective long-term treatments that reduce the need for corticosteroids are needed for Crohn's disease. Although purine antimetabolites are moderately effective for maintenance of remission patients often relapse despite treatment with these agents. Methotrexate may provide a safe and effective alternative to more expensive maintenance treatment with TNF-α antagonists.

Objectives

To conduct a systematic review of randomized trials examining the efficacy and safety of methotrexate for maintenance of remission in Crohn's disease.

Search methods

The Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2009, PUBMED (1966 to April 2009), EMBASE (1984 to April 2009), DDW abstracts (1980 to 2008) and the Cochrane IBD/FBD Specialized Trials Register were searched. Study references and review papers were also searched for additional trials.

Selection criteria

Randomised controlled trials (RCTs) that compared methotrexate to placebo or any other active intervention for maintenance of remission in Crohn's disease were eligible for inclusion.

Data collection and analysis

Data extraction and assessment of methodological quality of included studies were independently performed by each author. The main outcome measure was the proportion of patients maintaining clinical remission as defined by the studies and expressed as a percentage of the total number of patients randomized (intention to treat analysis). Pooled odds ratios and 95% confidence intervals were calculated for dichotomous outcomes.

Main results

Three studies were included in the review. A pooled analysis (n = 98) including one high quality trail (n = 76) showed that intramuscular methotrexate (15 mg/week) was significantly more effective than placebo for maintenance of remission in Crohn's disease (OR 3.11; 95% CI 1.31 to 7.41; P = 0.01). The number needed to treat to prevent one relapse was 4. A pooled analysis of two small studies (n = 50) showed no difference between methotrexate and 6-MP for maintenance of remission (OR 2.63; 95% CI 0.74 to 9.37; P = 0.14). Adverse events were generally mild in nature and resolved upon discontinuation or with folic acid supplementation. Common adverse events included nausea and vomiting, symptoms of a cold, abdominal pain, headache, joint pain or arthralgia, and fatigue.

Authors' conclusions

Intramuscular methotrexate at a dose of 15 mg/week is safe and effective for maintenance of remission in Crohn's disease. Oral methotrexate (12.5 to 15 mg/week) does not appear to be effective for maintenance of remission in Crohn's disease.

摘要

背景

Methotrexate維持克隆氏症的緩解狀態

克隆氏症(Crohn's disease)需要安全有效的長期療法,以減少病人對於皮質類固醇的需求。嘌呤的抗代謝劑對於維持克隆氏症的緩解狀態具有適度的效果,但是儘管病人接受這些藥物治療疾病還是經常復發。除了以較昂貴的TNFα拮抗劑作為維持治療之外,methotrexate可提供另一種安全且有效的治療選擇。

目標

對於評估methotrexate維持克隆氏症緩解狀態之功效及安全性的隨機試驗,進行系統性的回顧。

搜尋策略

我們搜尋了Cochrane Central Register of Controlled Trials(CENTRAL, Issue 2, 2009)、PUBMED(1966年到2009年4月)、EMBASE(1984年到2009年4月)、DDW摘要(1980年到2008年)及Cochrane IBD/FBD Specialized Trials Register等資料庫。同時,也搜尋了研究的參考文獻及回顧報告,以找尋其他的試驗。

選擇標準

比較以methotrexate與安慰劑或其他任何積極治療維持克隆氏症之緩解狀態的隨機對照試驗(randomised controlled trials;RCTs),都具有收納的資格。

資料收集與分析

由每一位作者獨立進行收納研究之數據摘錄及試驗方法品質的評估。主要結果測量值為依照研究定義之維持臨床緩解狀態的病人比例,並以這些病人佔隨機化的病人總數之百分比表示(意向治療分析)。計算二元化結果之合併危險對比值及95%信賴區間。

主要結論

本回顧中包含了3項研究。合併的分析(n = 98)中,包含了1項高品質的試驗(n = 76),該研究顯示,肌肉內注射methotrexate(15 mg/週)維持克隆氏症緩解狀態的效果,比安慰劑更明顯(OR 3.11; 95% CI 1.31 to 7.41; P = 0.01)。需要治療以防止疾病復發的病人人數為4人。以2項小型研究進行合併分析(n = 50),並未發現methotrexate和6MP維持病人緩解狀態的效果有所差異(OR 2.63; 95% CI 0.74 to 9.37; P = 0.14)。不良反應本質上通常是輕微的,停止用藥或補充葉酸後就可緩解。常見的不良反應包括噁心和嘔吐、出現感冒症狀、腹部疼痛、頭痛、關節疼痛或關節痛和疲勞。

作者結論

肌肉內注射15 mg/週的methotrexate劑量,對於克隆氏症是安全且有效的。口服methotrexate(12.5到15 mg/週)似乎無法有效地維持克隆氏症的緩解狀態。

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

Methotrexate可治療非活動性的克隆氏症。克隆氏症是腸道發生的慢性發炎性疾病,經常發生於小腸的下半段,也就是迴腸部分。然而,克隆氏症可能侵犯消化道的任何部分,從口腔到肛門都可能受到影響。最常見的症狀是腹部疼痛和腹瀉。Methotrexate是一種可以抑制身體自然免疫反應的藥物,也可以抑制與克隆氏症有關的發炎。本篇回顧顯示,肌肉內注射(即注射至手臂或大腿的肌肉)methotrexate(15 mg/週)40週,對於接受較高劑量之methotrexate(25 mg/週)後,可使疾病變得非活動性的病人而言,是防止克隆氏症復發的有效療法。Methotrexate造成的副作用本質上通常是輕微的,包括噁心和嘔吐、出現感冒症狀、腹部疼痛、頭痛、關節痛和疲勞。研究並未證實口服methotrexate(12.5到15 mg/週)可以有效地治療非活動性克隆氏症。不過,針對這種服藥方式進行的相關研究並不多。

Plain language summary

Methotrexate for treatment of inactive Crohn's disease

Crohn's disease is a chronic inflammatory disease of the intestines that frequently occurs in the lower part of the small intestine, called the ileum. However, Crohn’s disease can affect any part of the digestive tract, from the mouth to the anus. The most common symptoms are abdominal pain and diarrhea. Methotrexate is a drug that suppresses the body's natural immune responses and may suppress inflammation associated with Crohn’s disease. This review shows that methotrexate (15 mg/week) injected intramuscularly (i.e. into muscles located in the arm or thigh) for 40 weeks is an effective treatment for preventing relapse (return of disease symptoms) among patients whose disease became inactive while taking higher doses of intramuscular methotrexate (25 mg/week). Side effects occurred in a small number of patients. These side effects are usually mild in nature and include nausea and vomiting, cold symptoms, abdominal pain, headache, joint pain and fatigue. Methotrexate (12.5 to 15 mg/week) taken orally has not been shown to be effective treatment for inactive Crohn's disease. However, there has been little study of this approach.

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